Ultrasound-guided lymph node sampling: accuracy of FNAC, end-cutting (Franseen), and side-cutting (Temno) needle biopsy techniques.

AIM: To compare technical success, diagnostic accuracy, and histological yield of fine-needle aspiration cytology (FNAC), side-cutting (Temno) needle biopsy, and end-cutting (Franseen) needle biopsy for ultrasound-guided sampling of groin and axillary lymph nodes. MATERIALS AND METHODS: A total of 270 abnormal groin and axillary nodes were sampled using one of the three techniques. Nodes with a maximum length of <2.5 cm underwent FNAC or Franseen biopsy, while nodes >2.5 cm underwent Temno biopsy. Mean size of nodes sampled by FNAC (21.2 mm) and Franseen (19.7 mm) were similar while nodes sampled by Temno were larger (34.4 mm, p<0.0001). RESULTS: Technical success rates of FNAC (82/93, 88%), Franseen (105/111, 95%), and Temno (59/66, 89%) biopsies were similar (p>0.05 for all). Lymphoid tissue yield by FNAC (mean total area 1.51 mm2) was less than that by Franseen (7.14 mm2, p=0.002) or Temno biopsy (19.44 mm2, p<0.0001). Diagnostic accuracy for malignancy was lower for FNAC (22/30, 73%) than Franseen (25/26, 96%, p=0.02) or Temno biopsy (32/32, 100%, p=0.002). For malignant nodes, determining the likely organ of origin was also lower for FNAC (7/30, 23%) than Franseen (19/26, 73%, p=0.0002) or Temno biopsy (29/32, 91%, p<0.0001), with a similar pattern observed in the identification of lymphoma. CONCLUSION: For similarly sized nodes, Franseen biopsy provided more lymphoid material, a higher diagnostic accuracy for malignancy including lymphoma, and better identification of the likely organ of origin than FNAC. Routine use of Franseen biopsy is advocated rather than FNAC for percutaneous sampling of lymph nodes not suitable for side-cutting needle biopsy.

Current and future international patterns of care of neurogenic bladder after spinal cord injury.

PURPOSE: We aim to summarize the literature on international patterns of care for patients with neurogenic bladder (NGB) from spinal cord injury (SCI). METHODS: We performed a PubMed database search, hand review of references, communication with professional societies, and registry evaluations for pertinent data. RESULTS: Established patterns of care, including SCI registries and specialty centers, are available in high-resource countries such as the US and UK. As such, mortality rates from complications of NGB/SCI are lower. Access to intermittent catheterization supplies, among other resources, may be inadequate in many low-income regions. Cultural and religious beliefs may also hinder integration of proper bladder management in SCI patients. While guidelines exist in many parts of the world, it is unclear how rigorously they are disseminated or followed. CONCLUSIONS: While there is a paucity of high-level evidence, the differences in patterns of care are closely related to socioeconomic status and resources of the geographic area. Future research efforts should focus on improving access to diagnostic modalities, supplies, and specialists in these areas.

Ultrasound carpal tunnel syndrome: additional criteria for diagnosis.

AIM: To define the usefulness of the cross-sectional area (CSA) of the median nerve distal to the carpal tunnel in addition to other established common parameters in the diagnosis of carpal tunnel syndrome (CTS). MATERIALS AND METHODS: Forty-four wrists from 24 symptomatic CTS patients and 32 wrists from 17 asymptomatic volunteers were evaluated by ultrasound. The CSA of the median nerve was measured at four pre-selected levels, i.e., proximal, inlet, outlet, and distal to the carpal tunnel. The flattening ratio, intraneural vascularity, neural fasciculation, and retinacular palmar bowing were also assessed. RESULTS: Significant differences were found between the CTS and control groups for median nerve CSA proximal and distal (p<0.001) to the tunnel as well as retinacular bowing (p<0.001). Using the receiver operating characteristic (ROC) curve, the sensitivity, specificity, and accuracy of using a cut-off of >14 mm2 of CSA proximal and distal to the tunnel were 75%, 87.5%, 86.8% and 63.6%, 100%, 78.9%, respectively. Using either CSA proximal or distal to the tunnel or bowing retinaculum at the outlet >1 mm yielded a sensitivity, specificity, and accuracy of 100%, 84.3% and 93.4%, respectively. CONCLUSION: The median nerve CSA proximal and distal to the carpal tunnel and bowing of the retinaculum at the outlet are helpful in diagnosis of CTS.

Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment.

BACKGROUND: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. METHODS: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. RESULTS: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. CONCLUSIONS: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.

Nonlocal dark solitons under competing cubic-quintic nonlinearities.

We investigate properties of dark solitons under competing nonlocal cubic-local quintic nonlinearities. Analytical results, based on a variational approach and confirmed by direct numerical simulations, reveal the existence of a unique dark soliton solutions with their width being independent of the degree of nonlocality, due to the competing cubic-quintic nonlinearities.

A 5-year retrospective analysis of 5α-reductase inhibitors in men with benign prostatic hyperplasia: finasteride has comparable urinary symptom efficacy and prostate volume reduction, but less sexual side effects and breast complications than dutasteride.

OBJECTIVE: We evaluated 5-year safety, efficacy and prostate volume data from BPH patients treated with finasteride or dutasteride. METHODS: A retrospective analysis of 378 consecutive men treated with 5α-reductase inhibitor monotherapy between January 2004 and September 2009 (197 on finasteride and 211 on dutasteride) in a single clinic was performed. Efficacy assessments included International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), postvoid residual urine volume (PVR), prostate-specific antigen (PSA) and prostate volume (PV). Safety assessments included International Index of Erectile Function (IIEF) and adverse events. Patients were evaluated at 3 months, 1 year and yearly thereafter. RESULTS: Mean age of the group was 58.7 ± 6.7 years. Maintenance of therapy at 5 years was 57.4% and 42.5% for the finasteride and dutasteride groups respectively. Changes in IPSS, Qmax, PVR, PV and PSA were similar for both groups at 5 years. The incidence of erectile dysfunction, ejaculatory dysfunction and decreased libido resulting in discontinuation from therapy was significantly (p < 0.01) higher in the dutasteride (5.1%, 2.4%, 2.7% respectively) compared with the finasteride (2.1%, 1.8%, 1.4% respectively) group. In addition, the incidence of self-reported breast tenderness and/or enlargement was significantly (p < 0.01) greater in the dutasteride (3.5%) compared with the finasteride (1.2%) group. CONCLUSIONS: In this retrospective analysis of data from consecutive patients treated at a single clinic, both finasteride and dutasteride were effective therapies for the management of lower urinary tract symptoms. However, dutasteride resulted in significantly more sexual side effects and breast complications than finasteride.

Non-classical light state transfer in su(2) resonator networks.

We use a normal mode approach to show full and partial state transfer in a class of coupled resonator networks with underlying su(2) symmetry that includes the so-called [Formula: see text] photonic lattice. Our approach defines an auxiliary Hermitian coupling matrix describing the network that yields the normal modes of the system and its time evolution in terms of orthogonal polynomials. Our results provide insight on the full quantum state reconstruction time in a general su(2) network of any size and the full quantum transfer time in the [Formula: see text] network of size [Formula: see text] with [Formula: see text] For any other network sizes, the Fock state probability distribution of the initial state is conserved but the amplitudes suffer a phase shift proportional to [Formula: see text] that results in partial quantum state transfer.

Tissue-based molecular markers for renal cell carcinoma.

Since the introduction of targeted therapies in renal cell carcinoma (RCC), more individualized treatment options have become available. Molecular markers might support treatment planning due to more accurate individual risk stratification. Current molecular markers in RCC were reviewed to elucidate clinical impact and future perspectives. An English-language literature review of the Medline database (1990 to September 2010) of published data on tissue-based molecular markers and RCC was undertaken. Histological types, clinical and oncological behaviour are variable in renal masses. Molecular markers offer potential for additional information in tumour detection and diagnosis, prognostic and predictive values, as well as determination of therapeutic targets. Investigations on molecular biomarkers in RCC include hypoxia inducible factor (HIF-α), vascular endothelial growth factor (VEGF), carbonic anhydrase IX (CAIX), mammalian target of rapamycin (mTOR), survivin, B7-H1, p53, matrix metalloproteinases (MMP), Insulin-like growth factor II mRNA-binding protein 3 (IMP3), Ki-67, C-reactive protein (CRP), Vimentin, Fascin, platelet count, hemoglobin level and combinations of these factors. Although some markers offer promising results, utilization in daily practice is compromised due to limited specificity, predictive accuracy and tumour histology variablity. There is an imminent need for novel molecular markers that allow accurate histologic and biologic classification of RCC to improve upon current outcomes. It is very likely that a panel of molecular markers will be used to achieve a sufficient degree of certainty in order to guide clinical decisions. A large concerted effort is required to advance the field of RCC molecular marker through systematic discovery, verification, and validation.

Tissue-based molecular markers for bladder cancer.

Bladder cancer is the second most common genitourinary malignancy in the United States, and is a major cause of morbidity and mortality. Despite aggressive treatment, survival for patients with muscle-invasive urothelial carcinoma of the bladder remains poor. Cancer stage, grade, and other clinical and pathological characteristics provide only limited prognostic information, and there is significant heterogeneity in patient outcomes using current risk stratification. Recent research into the profiling of bladder cancer at the molecular level has begun to shed light on important mechanisms of pathogenesis, as well as providing a number of potential tissue markers. These may provide useful prognostic information and guide patient selection for therapeutic strategies. This review explores recent advances in tissue-based molecular markers in bladder cancer and their potential utility. We also discuss design and statistical consideration for development and validation of molecular markers. A combination of complementary and yet independent molecular markers will likely better capture the biologic potential of each individual bladder tumor resulting in improved clinical decision-making.

Implications of the Revisions and Revaluation of Office/Outpatient Evaluation and Management Codes for Neuroradiology Reimbursement.

In the 2020 Final Rule, the Center for Medicare & Medicaid Services adopted a new coding structure and accepted the substantial increase in valuation for office/outpatient Evaluation and Management codes set to begin in 2021. Given budget neutrality requirements, the projected increase in reimbursement will require a reduction in the conversion factor to offset such increases. The aim is to inform neuroradiologists the impact of these proposed changes on reimbursement and the profession.

Prevention of vertebrate neuronal death by the crmA gene.

Interleukin-1 beta converting enzyme (ICE) is a mammalian homolog of CED-3, a protein required for programmed cell death in the nematode Caenorhabditis elegans. The activity of ICE can be specifically inhibited by the product of crmA, a cytokine response modifier gene encoded by cowpox virus. Microinjection of the crmA gene into chicken dorsal root ganglion neurons was found to prevent cell death induced by deprivation of nerve growth factor. Thus, ICE is likely to participate in neuronal death in vertebrates.

Compartmentalization of acetylcholinesterase mRNA and enzyme at the vertebrate neuromuscular junction.

Acetylcholinesterase (AChE) is concentrated at the vertebrate neuromuscular synapse. To determine whether increased transcript levels could underlie this selective accumulation, we employed a quantitative reverse transcription polymerase chain reaction-based assay to determine mRNA copy number in samples as small as single neuromuscular junctions (NMJs) and a microassay to measure AChE enzyme activity at single synapses. Our results show that AChE mRNA is an intermediate transcript at NMJs, whereas in noninnervated regions of muscle fibers, AChE transcripts are either undetectable or rare. In contrast, alpha-actin transcript levels in the same samples are similar in junctional and extrajunctional regions. However, compared with AChE enzyme activity and alpha-actin mRNA levels, the levels of AChE transcripts at NMJs are highly variable. These results indicate that AChE mRNA and protein expression are compartmentalized at the vertebrate NMJ and provide a direct approach toward dissecting the molecular events leading from synaptic activation to plastic changes in gene expression at single vertebrate synapses.

The Mauthner cell and other identified neurons of the brainstem escape network of fish.

This paper reviews the development of our research on the motor consequences of Mauthner cell function and related brainstem neurons. These cells activate fast-start responses such as seen in fishes escaping from predatory attacks. Our goal was to devise a neuroethological theory of fish escape that accurately reconciled the underlying neural function with a correct concept of the motor act. The identified neuron concept of invertebrates greatly influenced the initial studies. Horseradish peroxidase technology allowed us and other workers to identify principal neurons in the brainstem escape system. Digital imaging technology permitted adequate kinematic characterization of the behavior. Resulting experiments showed that Mauthner system demonstrates two general principles of motor organization: (1) the Mauthner cell is a command-like higher order neuron that serially outputs to a lower level central pattern generator; and (2) the Mauthner cell participates in a larger parallel, brainstem escape network. In this network, we showed that the spatio-temporal pattern of activity codes the timing and magnitude of agonist and antagonist trunk muscle contractions during the behavior. Because the approach angle of the stimulus determines these parameters, we were able to discover the overall sensorimotor relationship between stimulus angle and motor output. This relationship is given as a set of descriptive equations written in terms of stimulus angle, magnitude and timing variables of trunk muscle contractions, and resulting escape trajectory. The equations unify the apparent variability of C-start movement patterns into a single, quantitative theory. Recent studies by other workers show how this concept can make accurate predictions about the underlying neural processes, even at the level of the single, identified cell.

Azidothymidine and interferon-alpha induce apoptosis in herpesvirus-associated lymphomas.

Lymphoproliferative diseases that occur in immunocompromised patients are frequently associated with herpesviruses. These patients often fare poorly after treatment with conventional chemotherapy. We reported previously that patients with AIDS-related Burkitt's lymphoma (BL) responded to parenteral azidothymidine (AZT) and IFN-alpha. We found that EBV-positive lymphoma cells derived from these patients cultured with AZT express CD95 and undergo apoptosis. AZT-mediated apoptosis was caspase dependent and occurred despite Fas receptor blockade. In contrast, EBV-negative lymphomas were resistant to AZT-induced apoptosis, as were EBV-positive lymphomas that expressed high levels of bcl-2. Primary effusion lymphoma (PEL) cell lines infected with human herpesvirus type 8 required IFN-alpha to potentiate AZT-induced apoptosis. IFN-alpha did not up-regulate CD95 in BL or PEL but did induce expression of the death receptor ligand, CD95 ligand. AZT-sensitive lymphomas also accumulated significantly higher intracellular AZT monophosphate than did resistant lymphomas. Our data demonstrated distinct apoptotic responses to AZT and IFN-alpha in herpesvirus-associated lymphomas. EBV-positive BL cells that expressed low BCL-2 levels were sensitive to AZT alone; PEL cells required the addition of IFN-alpha to enhance apoptosis, and EBV-negative lymphomas were insensitive to both agents. AZT-sensitive BL cells transfected with BCL-2 became resistant. Susceptibility to antivirus-mediated apoptosis may be exploited to improve the therapy of certain herpesvirus-associated lymphomas.

Long-term outcomes of neovascular glaucoma treated with and without intravitreal bevacizumab.

AIMS: To compare the outcomes of neovascular glaucoma (NVG) treated with and without intravitreal bevacizumab in a large case comparison study. METHODS: The study is a retrospective, comparative, case series of 163 eyes of 151 patients with NVG, including 99 treated without and 64 treated with intravitreal bevacizumab. Medical and surgical treatments for NVG were assessed. The main outcome measures were visual acuity (VA) and intraocular pressure (IOP). RESULTS: At the time of NVG diagnosis, the median VA was count fingers (CF) in the non-bevacizumab group and 2/300 in the bevacizumab group. IOP (mean±SD) was 43.1±13.0 mm Hg in the non-bevacizumab group and 40.8±11.5 mm Hg in the bevacizumab group. IOP (mean±SD) decreased to 18.3±13.8 mm Hg in the non-bevacizumab group and 15.3±8.0 mm Hg in the bevacizumab group, and the median VA was CF in both treatment groups at a mean follow-up of 12 months. Panretinal photocoagulation (PRP) substantially reduced the need for glaucoma surgery (P<0.001) in bevacizumab treated NVG eyes. CONCLUSIONS: Although bevacizumab delayed the need for glaucoma surgery, PRP was the most important factor that reduced the need for surgery. Vision and IOP in eyes with NVG treated with bevacizumab showed no long-term differences when compared with eyes that were not treated with bevacizumab. Thus, intravitreal bevacizumab serves as an effective temporizing treatment, but is not a replacement for close monitoring and definitive treatment of NVG. PRP remains the treatment modality that affects the course of NVG in terms of decreasing the need for surgery to control IOP.

Regulation of Fas-dependent activation-induced T cell apoptosis by cAMP signaling: a potential role for transcription factor NF-kappa B.

TCR-mediated activation of T cell hybridomas induces programmed cell death by a Fas-dependent pathway. We now show that costimulation of 2B4 cells, in the absence or presence of transgenic Bcl-2, with anti-CD3 epsilon and forskolin, an activator of cAMP signaling, resulted in antagonism of Fas-dependent activation-induced cell death that was always accompanied by selective downregulation of the nuclear levels of NF-kappa B p65-p50 (RelA-p50) transcription factor. Forskolin not only inhibited activation-induced cell death and NF-kappa B activation, but also suppressed expression of Fas and Fas ligand (Fas-L). Furthermore, NF-kappa B p65 antisense oligonucleotide down-regulated nuclear levels of NF-kappa B, inhibited cell surface expression of Fas-L and apoptosis of 2B4. Collectively, these finding demonstrate a potential role of NF-kappa B in the regulation of activation-induced apoptosis in T lymphocytes.

Identification of a novel platelet-derived growth factor-like gene, fallotein, in the human reproductive tract.

We isolated the cDNA of a novel platelet-derived growth factor-like gene from human endometrium. The gene was named fallotein; it was 3007 bases in length, and encoded a protein of 345 amino acids. Antiserum against the fallotein protein can recognize a specific protein in the fallopian tube, with a molecular size in accordance with the anticipated size of fallotein. Fallotein mRNA is expressed in two molecular sizes, 3.8 and 2.9 kb, with the former being more abundant. High expression of the gene was found in the prostate, testis, and uterus. A weaker expression signal was found in the spleen, thymus, and small intestine, but expression of fallotein in the colon and peripheral blood leukocytes was negligible.

A phase diagram of the binding of mismatched duplex DNAs to hydroxyapatite.

The hydroxyapatite binding properties of imperfectly base-paired DNA have been investigated and summarized in a phase diagram. This diagram defines the conditions at which thermal elution results in both denaturation and desorption of mismatched duplex DNA from hydroxyapatite.

Ultra-short metformin pretreatment for clomiphene citrate-resistant polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of ultra-short (12 days) metformin pretreatment in clomiphene-citrate (CC) resistant polycystic ovary syndrome (PCOS). METHOD: Eighty women with CC-resistant PCOS were randomly allocated to metformin pretreatment or usual treatment. Forty women received 1500 mg metformin daily for 12 days, followed by clomiphene 150 mg daily for 5 days along with metformin. Forty women (control group) received the same dose of clomiphene but no metformin pretreatment. RESULTS: In the metformin group, 17 (42.5%) women ovulated, and 6 (15%) conceived. In the control group, 5 (12.5%) women ovulated but none conceived. Compared with the control group, the metformin group had significantly higher ovulation (P = 0.03) and pregnancy rates (P = 0.026). CONCLUSION: Twelve days of metformin pretreatment improves ovulation and pregnancy rates in women with CC-resistant PCOS.

Identifiable reticulospinal neurons of the adult zebrafish, Brachydanio rerio.

Reticulospinal neurons of the larval zebrafish Brachydanio rerio have been categorized into 27 different types (Kimmel et al.: Journal of Comparative Neurology 205:112-127, 1982; Metcalfe et al.: Journal of Comparative Neurology 251:147-159, 1986). Nineteen of these occur as bilateral pairs which are individually identifiable. Since considerable remolding of brain structures (e.g., cell death and modifications of neuronal architecture) occurs during development, we ask if these cells are preserved in the adult zebrafish and the extent to which neuronal morphology of the larva is conserved during ontogeny. In our analysis, we studied reticular neurons from 84 brains retrogradely labelled from the spinal cord with HRP. We show that all reticulospinal types of the larva are retained without considerable change in morphology in the adult. Many neurons, including the Mauthner cell and two of its serial homologues, MiD2cm and MiD3cm, can be individually and unambiguously identified. In addition, the appearance of later developing (tertiary) neurons leads to an increase in the numbers of some neuron types. Although tertiary neurons are often isomorphic with neighboring cells, they can have unique morphologies of their own and, therefore, are also individually identifiable. We suggest that the appearance of tertiary neurons may serve to extend the behavioural repertoire of the embryo. Moreover, morphological repetitions in adjacent segments of the otic region (level of VIIIth nerve entry) may represent the replication of a functional motif, perhaps involving the C-type escape response which is known to involve the Mauthner cell.